CA2531897C - Catheter with sheathed hypotube - Google Patents

Catheter with sheathed hypotube Download PDF

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Publication number
CA2531897C
CA2531897C CA2531897A CA2531897A CA2531897C CA 2531897 C CA2531897 C CA 2531897C CA 2531897 A CA2531897 A CA 2531897A CA 2531897 A CA2531897 A CA 2531897A CA 2531897 C CA2531897 C CA 2531897C
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CA
Canada
Prior art keywords
tubular member
distal outer
end region
catheter assembly
catheter
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CA2531897A
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French (fr)
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CA2531897A1 (en
Inventor
Tracee Eidenschink
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boston Scientific Ltd Barbados
Original Assignee
Boston Scientific Ltd Barbados
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Filing date
Publication date
Application filed by Boston Scientific Ltd Barbados filed Critical Boston Scientific Ltd Barbados
Publication of CA2531897A1 publication Critical patent/CA2531897A1/en
Application granted granted Critical
Publication of CA2531897C publication Critical patent/CA2531897C/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/10Balloon catheters
    • A61M25/104Balloon catheters used for angioplasty
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/0021Catheters; Hollow probes characterised by the form of the tubing
    • A61M25/0023Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
    • A61M25/0026Multi-lumen catheters with stationary elements
    • A61M25/0032Multi-lumen catheters with stationary elements characterized by at least one unconventionally shaped lumen, e.g. polygons, ellipsoids, wedges or shapes comprising concave and convex parts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00Catheters; Hollow probes
    • A61M25/01Introducing, guiding, advancing, emplacing or holding catheters
    • A61M2025/0183Rapid exchange or monorail catheters

Abstract

A catheter assembly and method for constructing same comprises the engagement of a substantially hollow proximal tubular member, which is at least partially coated with at least one polymeric material, to a substantially distal outer tubular member. The proximal tubular member and the distal outer tubular member define at least one continuous central lumen therethrough. At least a portion of the distal outer tubular member is disposed about at least a portion of an inner tubular member. A portion of the inner tubular member is engaged to a portion of the proximal tubular member. A portion of the inner tubular member is engaged to a portion of the end region of the distal outer member. An end region of the proximal tubular member extends distally into the distal outer tubular member adjacent to the inner tubular member.

Description

TITLE

Catheter with Sheathed Hypotube BACKGROUND OF THE INVENTION
Field of the Invention The present invention is directed to a variety of embodiments. At least one embodiment of the invention is directed to the field of intravascular medical devices, and more particularly to the field of catheters such as angioplasty, neurological and guide catheters, among others, which may be used in various medical procedures such as percutaneous transluminal angioplasty (PTA), percutaneous transluminal coronary angioplasty (PTCA) as well as in procedures involving the placement of medicines and medical devices within the body.

Some embodiments of the invention are directed to all forms of catheters which may be advanced through a body lumen or vessel. Some examples of catheters are over-the-wire (OTW) catheters, such as are described in US 5047045; single-operator-exchange (SOE) balloon catheters, such as are described in US 5156594 and US
5549552. Other examples of catheters which may incorporate the unique features of the present invention include rapid-exchange style balloon catheters, MONORAIL

dilatation catheters available from SciMed Life Systems, Inc. of Maple Grove, Minnesota, etc.

Description of the Related Art:
Intravascular diseases are commonly treated by relatively non-invasive techniques such as PTA and PTCA. These angioplasty techniques typically involve the use of a balloon catheter. In these procedures, a balloon catheter is advanced through the vasculature of a patient such that the balloon is positioned proximate a constriction in a diseased vessel. The balloon is then inflated and the constriction in the vessel is opened. In other uses a catheter may be used to deliver an endoprosthesis such as a stent, graft, stent-graft, filter or other implantable or optionally implantable device or devices herein after collectively referred to as a stent or stents. Where a stent is to be delivered into a body lumen the catheter may include one or more inflatable portions or balloons.
Typically, the stent is retained in the predelivery state about the catheter shaft, or a portion thereof such as a balloon, by crimping and/or through the use of a retaining mechanism such as sleeve, sheath or sock.
Balloons and balloon catheters may be particularly useful for the delivery of stents. Stents and catheters used in their delivery are commonly used and as such their structure and function are well known.
Many rapid exchange catheters, including some types of balloon catheters, comprise a proximal portion, often include a hypotube which can be constructed from a variety of non-thermoplastic and/or metallic material(s). This hypotube is joined to a distal outer shaft portion of the catheter at a port area by using a mid-shaft tube that connects the catheter sections together. Typically, the outer shaft is at least partially constructed of a polymer substance. The port area is the area of the catheter where the proximal guide wire exits the catheter assembly such as is shown in the PRIOR
ART
drawing labeled FIG. 1. A core wire or other member can aid in support of the mid-shaft area.
A goal of the present invention is to provide a more simplified and efficient catheter assembly design that avoids the necessity of a mid-shaft tube to link the distal outer to the hypotube, as well as to avoid the use of a core wire.
Without limiting the scope of the invention a brief summary of some of the claimed embodiments of the invention is set forth below. Additional details of the summarized embodiments of the invention and/or additional embodiments of the invention may be found in the Detailed Description of the Invention below.
A brief abstract of the technical disclosure in the specification is provided as well. The abstract is not intended to be used for interpreting the scope of the claims.

BRIEF SUMMARY OF THE INVENTION

As indicated above, the present invention may be embodied in a variety of forms. In at least one embodiment the invention is directed to a catheter assembly which avoids the use of a mid-shaft tube by directly engaging the proximal shaft portion or hypotube directly to the distal outer by providing at least a distal portion of the hypotube with a polymeric sheath which may be bonded directly to the distal outer.
Where a guide wire port is required, a portion of the sheath is bonded to the distal outer and a portion is bonded to the inner shaft which defines the proximal guide wire port.
In some embodiments a portion of the hypotube extends distally a predetermined length beyond the guide wire port. In this manner the hypotube supports the mid-shaft region of the catheter without the need of an additional mind-shaft tube or core wire support.

In at least one embodiment the hypotube sheath comprises one or more materials such as polyesters; polyurethanes; polyamides; polyolefins including polyethylene and polypropylene; and any copolymers thereof. Some more specific examples of suitable materials include, but are not limited to: nylon;
polyester elastomer; polyether/block polyamide, such as Pebax, Hytrel, and/or Arnitel;
polyamid such as Grilamid; flouro-polymer, such as Kynar; polyether ether ketone (PEEK);
polyethylene (PE); polyurethane; polyolefin copolymer (POC);
tetrafluoroethylenes, such as polytetrafluoroethylene (PTFE); etc.

These and other embodiments which characterize the invention are pointed out with particularity in the claims annexed hereto and forming a part hereof.
However, for a better understanding of the invention, its advantages and objectives obtained by its use, reference should be made to the drawings which form a further part hereof and the accompanying descriptive matter, in which there is illustrated and described a embodiments of the invention.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S) A detailed description of the invention is hereafter described with specific reference being made to the drawings.

FIG. 1 is a longitudinal side view of a mid-shaft region of a catheter assembly which is representative of a PRIOR ART assembly.
FIG. 2 is a longitudinal side view of an embodiment of the invention.
FIG. 3 is a perspective side view of a hypotube configuration suitable for use in the embodiment shown in FIG. 2.

FIG. 4 is a cross-sectional view of the embodiment shown in FIG. 2;
FIG. 5 is a side elevational view of a balloon dilation catheter with the embodiment of FIG. 2.
FIG. 6 is a cross-sectional view of the embodiment shown in FIG. 2 with a butt-weld engagement between the outer shaft and the coating.

DETAILED DESCRIPTION OF THE INVENTION
While this invention may be embodied in many different forms, there are described in detail herein specific preferred embodiments of the invention.
This description is an exemplification of the principles of the invention and is not intended to limit the invention to the particular embodiments illustrated.
For the purposes of this disclosure, like reference numerals in the figures shall refer to like features unless otherwise indicated.
As indicated above, FIG. 1 shows a longitudinal cross-section of a PRIOR
ART catheter assembly 100, which employs a mid-shaft tube 110 to connect the proximal shaft or hypotube 112 and distal outer 114. The mid-shaft tube 110 is welded, bonded or otherwise engaged to the proximal shaft 112 via a polymeric coating 117. The mid-shaft tube 110 supports the inner shaft 122 which defines a proximal guide wire lumen 124. A
core wire 120 extends through an inflation lumen 126 defined by the hypotube 112 to provide further support and reinforcement of the port bond 118 of the mid-shaft region shown.
In at least one embodiment of the present invention a catheter assembly, indicated generally at 10 in FIG. 2, is assembled without employing a mid-shaft tube and/or a core wire such as previously described. The catheter assembly may be a balloon catheter 10, as illustrated in FIG. 5.
In the embodiment shown in FIG. 2 a proximal shaft or hypotube 12 includes a sheath or coating 14 of one or more polymeric materials such as polyesters;

polyurethanes; polyamides; polyolefins including polyethylene and polypropylene; and any copolymers thereof. Some more specific examples of suitable materials include, but are not limited to: nylon; polyester elastomer; polyether/block polyamide, such as Pebax, Hytrel, and/or Amitel; polyamid such as Grilamid; flouro-polymer, such as Kynar;
5 polyether ether ketone (PEEK); polyethylene (PE); polyurethane; polyolefin copolymer (POC); tetrafluoroethylenes, such as polytetrafluoroethylene (PTFE); etc.

Coating 14 may be applied to the external surface 16 of at least a portion of the hypotube 12, or may be a tubular member of material disposed thereabout. In some embodiments the hypotube 12 is at least partially constructed from one or more non-thermoplastic polymers and/or metal. In the embodiment shown, at least one side, of the distal end, of the hypotube 12 is engaged to the interior surface 22 of the distal outer shaft 20, in an overlapping configuration. The coating 14 is welded or otherwise bonded to the distal outer shaft 20. The coating 14 may form a continuous polymeric layer of material with the distal outer shaft 20. In some embodiments the distal outer shaft 20 radially overlaps at least a portion of the coating 14, or alternatively the coating 14 radially overlaps at least a portion of the distal outer shaft 20. In at least one embodiment an end-to-end (butt-weld) engagement configuration (48) is provided between the outer shaft 20 and the coating 14, as shown in FIG. 6.

As illustrated in FIG.2, the catheter assembly 10 has three engagement regions 42, 44 and 46. The engagement of the hypotube 12 and the distal outer shaft 20 forms a first engagement region 42. The engagement of the hypotube 12 and the inner shaft 24 forms a second engagement region 44. The engagement of the inner shaft 24 and the outer shaft 20 forms a third engagement region 46.
Depending on the material selected for coating 14, the coating 14 may act as a lubricious polymer shrinkable tube that is suitable for thermal welding of polymers of the adjacent structures.
In at least one embodiment the hypotube 12 is at least partially constructed of one or more metals such as stainless steel, titanium, nickel, and/or alloys thereof. The distal end of the hypotube 12 may extend beyond the region where the distal outer is bonded to the hypotube 12 via coating 14 to provide greater radial support to the port bond 18 and push strength to the catheter 10. Because only a portion of the hypotube 12 is bonded to the distal outer shaft 20 as previously described, flexibility of the port bond region is enhanced.
In addition to allowing the distal outer shaft 20 to be directly engaged to the hypotube 12, the coating 14 similarly provides for direct engagement of the inner shaft 24 to at least one side of the hypotube 12 as well. As is shown in FIG.
2 the inner shaft 24 defines a lumen 26 through which a guide wire 28 is passed. Inner shaft 24 also defines the port 29 where the guide wire 28 exits the catheter 10.

Due to the presence of the hypotube 12 underlying the port bond 18 of the catheter 10, the coated hypotube 12 may be directly engaged to the distal outer tube 20 by welding, bonding, physical engagement, or other engagement method(s) without the need of a mandrel or other support member.
In at least one embodiment the hypotube 12 is provided with sides 30 and 32 which are of equal or unequal length. Where one side 32 of the hypotube 12 is longer than other side 30, the longer side 32 acts in place of the core wire to provide strain relief.
As a result, the use of a core wire, such as has been previously described, is avoided in the present invention. As is shown in the embodiment depicted in FIG. 3, at least a portion of the hypotube 12 may be provided with one or more indentations, spaces or cuts 34 in a spiral, helical or other geometric configuration. By providing the hypotube 12 with a spiral cut 34 strain relief as well as flexibility is further enhanced.
In addition to the above, it is also noted that as the distal end of the hypotube 12 advances through the port bond 18 of the catheter the hypotube 12 is deformed or otherwise provided with a more elliptical cross-sectional shape, such as is shown in FIG. 4. The unique curvature of the hypotube 12 where it extends through the port bond allows the hypotube 12 to act as a supportive bridge or keystone in an arch to provide significant compression resistance to prevent collapse of the inflation lumen(s) 40.
While reference has been made to various preferred embodiments of the invention other variations, implementations, modifications, alterations and embodiments are comprehended by the broad scope of the appended claims. Some of these have been discussed in detail in this specification and others will be apparent to those skilled in the art. Those of ordinary skill in the art having access to the teachings herein will recognize these additional variations, implementations, modifications, alterations and embodiments, all of which are within the scope of the present invention and intended to be covered by the appended claims, without limitation.

Claims (37)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A catheter assembly comprising:
a substantially hollow proximal tubular member, at least a portion of the proximal tubular member having a coating of at least one thermoplastic polymer thereabout, the proximal tubular member having an end region, at least the end region having the coating of at least one thermoplastic polymer;

a substantially distal outer tubular member, the distal outer tubular member having an end region, a first portion of the end region of the distal outer tubular member being engaged to a first portion of the coating on a first portion of the end region of the proximal tubular member to define a first engagement region, the first engagement region comprising the first portion of the end region of the distal outer tubular member radially overlapping the first portion of the end region of the proximal tubular member, a first portion of the coating and the first portion of the end region of the distal outer tubular member being bonded together, the proximal tubular member and the distal outer tubular member defining at least one continuous central lumen therethrough; and a substantially hollow inner tubular member, at least a portion of the distal outer tubular member disposed about at least a portion of the inner tubular member, a first portion of the inner tubular member engaged to the coating on a second portion of the end region of the proximal tubular member to define a second engagement region, a second portion of the inner tubular member engaged to a second portion of the end region of the distal outer member to define a third engagement region, the end region of the proximal tubular member extending distally into the distal outer tubular member adjacent to the at least a portion of the inner tubular member.
2. The catheter assembly of claim 1 wherein the catheter assembly is a balloon catheter.
3. The catheter assembly of claim 1 wherein the catheter assembly is a monorail catheter or a rapid-exchange catheter.
4. The catheter assembly of claim 1 wherein the proximal tubular member is at least partially constructed from metal.
5. The catheter assembly of claim 1 wherein the coating is selected from at least one member of the group consisting of: nylon, polyester elastomer, polyether/block polyamide, polyamide, flouro-polymer, PEEK, PE, polyurethane, POC, PTFE and any combination thereof.
6. The catheter of claim 1 wherein the proximal tubular member is a hypotube.
7. The catheter of claim 1 wherein the distal outer tubular member is at least partially constructed from at least one polymeric material.
8. The catheter of claim 1 wherein the distal outer tubular member is at least partially constructed from at least one member of the group consisting of:
nylon, polyester elastomer, polyether/block polyamide, polyamide, flouro-polymer, PEEK, PE, polyurethane, POC, PTFE and any combination thereof.
9. The catheter assembly of claim 1 wherein a first portion of the coating and the first portion of the end region of the distal outer tubular member are bonded together in a continuous layer.
10. The catheter assembly of claim 1 wherein the inner member defines a guide wire lumen.
11. The catheter assembly of claim 1 wherein the inner member is at least partially constructed from at least one member of the group consisting of: nylon, polyester elastomer, polyether/block polyamide, polyamide, flouro-polymer, PEEK, PE, polyurethane, POC, PTFE and any combination thereof.
12. The catheter assembly of claim 1 wherein the proximal tubular member has a substantially elliptical cross-sectional shape.
13. A catheter assembly comprising:

a substantially hollow proximal tubular member, at least a portion of the proximal tubular member having a coating of at least one thermoplastic polymer thereabout, the proximal tubular member having an end region, at least the end region having the coating of at least one thermoplastic polymer;

a substantially distal outer tubular member, the distal outer tubular member having an end region, a first portion of the end region of the distal outer tubular member being engaged to a first portion of the coating on a first portion of the end region of the proximal tubular member to define a first engagement region, the first engagement region comprising the first portion of the end region of the distal outer tubular member radially overlapping the first portion of the end region of the proximal tubular member, a first portion of the coating and the first portion of the end region of the distal outer tubular member are welded together in a butt-weld configuration, the proximal tubular member and the distal outer tubular member defining at least one continuous central lumen therethrough; and a substantially hollow inner tubular member, at least a portion of the distal outer tubular member disposed about at least a portion of the inner tubular member, a first portion of the inner tubular member engaged to the coating on a second portion of the end region of the proximal tubular member to define a second engagement region, a second portion of the inner tubular member engaged to a second portion of the end region of the distal outer member to define a third engagement region, the end region of the proximal tubular member extending distally into the distal outer tubular member adjacent to the at least a portion of the inner tubular member.
14. The catheter assembly of claim 13 wherein the catheter assembly is a balloon catheter.
15. The catheter assembly of claim 13 wherein the catheter assembly is a monorail catheter or a rapid-exchange catheter.
16. The catheter assembly of claim 13 wherein the proximal tubular member is at least partially constructed from metal.
17. The catheter assembly of claim 13 wherein the coating is selected from at least one member of the group consisting of: nylon, polyester elastomer, polyether/block polyamide, polyamide, flouro-polymer, PEEK, PE, polyurethane, POC, PTFE and any combination thereof.
18. The catheter of claim 13 wherein the proximal tubular member is a hypotube.
19. The catheter of claim 13 wherein the distal outer tubular member is at least partially constructed from at least one polymeric material.
20. The catheter of claim 13 wherein the distal outer tubular member is at least partially constructed from at least one member of the group consisting of:
nylon, polyester elastomer, polyether/block polyamide, polyamide, flouro-polymer, PEEK, PE, polyurethane, POC, PTFE and any combination thereof.
21. The catheter assembly of claim 13 wherein the inner member defines a guide wire lumen.
22. The catheter assembly of claim 13 wherein the inner member is at least partially constructed from at least one member of the group consisting of: nylon, polyester elastomer, polyether/block polyamide, polyamide, flouro-polymer, PEEK, PE, polyurethane, POC, PTFE and any combination thereof.
23. The catheter assembly of claim 13 wherein the proximal tubular member has a substantially elliptical cross-sectional shape.
24. A catheter assembly comprising:
a substantially hollow proximal tubular member, the proximal tubular member having an end region;
a substantially distal outer tubular member, the distal outer tubular member having an end region, a first portion of the end region of the distal outer tubular member being engaged to a first portion of the end region of the proximal tubular member to define a first engagement region, the proximal tubular member and the distal tubular member defining at least one continuous central lumen therethrough; and a substantially hollow inner tubular member, at least a portion of the distal outer tubular member disposed about at least a portion of the inner tubular member, a first portion of the inner tubular member engaged to a second portion of the end region of the proximal tubular member to define a second engagement region, a second portion of the inner tubular member engaged to a second portion of the end region of the distal outer member to define a third engagement region, the end region of the proximal tubular member extending distally into the distal outer tubular member adjacent to the at least a portion of the inner tubular member;
characterized in that the proximal tubular member is a hypotube, and at least a distal portion of the proximal tubular member has a coating of at least one thermoplastic polymer thereabout, wherein the hypotube is directly engaged to the distal outer tubular member by bonding the coating directly to the distal outer tubular member, and wherein the distal end of the hypotube extends beyond the region where the distal outer tubular member is bonded to the hypotube via the coating.
25. The catheter assembly of claim 1 wherein the catheter assembly is a balloon catheter.
26. The catheter assembly of claim 1 wherein the catheter assembly is a monorail catheter or a rapid-exchange catheter.
27. The catheter assembly of claim 1 wherein the proximal tubular member is at least partially constructed from metal.
28. The catheter assembly of claim 1 wherein the coating is selected from at least one member of the group consisting of: nylon, polyester elastomer, polyether/block polyamide, polyamide, flouro-polymer, PEEK, PE, polyurethane, POC, PTFE and any combination thereof.
29. The catheter of claim 1 wherein the distal outer tubular member is at least partially constructed from at least one polymeric material.
30. The catheter of claim 1 wherein the distal outer tubular member is at least partially constructed from at least one member of the group consisting of:
nylon, polyester elastomer, polyether/block polyamide, polyamide, flouro-polymer, PEEK, PE, polyurethane, POC, PTFE and any combination thereof.
31. The catheter assembly of claim 1 wherein the first engagement region comprises the first portion of the end region of the distal outer tubular member radially overlapping the first portion of the end region of the proximal tubular member.
32. The catheter assembly of claim 31 wherein a first portion of the coating and the first portion of the end region of the distal outer tubular member are bonded together.
33. The catheter assembly of claim 31 wherein a first portion of the coating and the first portion of the end region of the distal outer tubular member are welded together in a butt-weld configuration.
34. The catheter assembly of claim 31 wherein a first portion of the coating and the first portion of the end region of the distal outer tubular member are fused together in a continuous layer.
35. The catheter assembly of claim 24 wherein the inner member defines a guide wire lumen.
36. The catheter assembly of claim 24 wherein the inner member is at least partially constructed from at least one member of the group consisting of: nylon, polyester elastomer, polyether/block polyamide, polyamide, flouro-polymer, PEEK, PE, polyurethane, POC, PTFE and any combination thereof.
37. The catheter assembly of claim 24 wherein the proximal tubular member has a substantially elliptical cross-sectional shape.
CA2531897A 2003-09-17 2004-07-23 Catheter with sheathed hypotube Expired - Fee Related CA2531897C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US10/664,132 2003-09-17
US10/664,132 US7367967B2 (en) 2003-09-17 2003-09-17 Catheter with sheathed hypotube
PCT/US2004/023809 WO2005035044A1 (en) 2003-09-17 2004-07-23 Catheter with sheathed hypotube

Publications (2)

Publication Number Publication Date
CA2531897A1 CA2531897A1 (en) 2005-04-21
CA2531897C true CA2531897C (en) 2012-09-25

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Application Number Title Priority Date Filing Date
CA2531897A Expired - Fee Related CA2531897C (en) 2003-09-17 2004-07-23 Catheter with sheathed hypotube

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US (1) US7367967B2 (en)
EP (1) EP1663378B1 (en)
JP (1) JP4637104B2 (en)
AT (1) ATE419032T1 (en)
CA (1) CA2531897C (en)
DE (1) DE602004018793D1 (en)
ES (1) ES2319301T3 (en)
WO (1) WO2005035044A1 (en)

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CA2531897A1 (en) 2005-04-21
EP1663378B1 (en) 2008-12-31
JP2007505683A (en) 2007-03-15
ES2319301T3 (en) 2009-05-06
DE602004018793D1 (en) 2009-02-12
JP4637104B2 (en) 2011-02-23
US20050059959A1 (en) 2005-03-17
US7367967B2 (en) 2008-05-06
WO2005035044A1 (en) 2005-04-21
EP1663378A1 (en) 2006-06-07
ATE419032T1 (en) 2009-01-15

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